Cognitive assessment in Huntington disease clinical drug trials

Abstract

Several Huntington disease (HD) clinical trials are in progress and on the horizon. Potential treatments are increasingly being targeted at ameliorating the cognitive decline in HD. This necessitates a careful consideration of trial designs, including endpoint strategies suitable for testing cognitive function. The aim of this chapter is to evaluate and consider the use of cognitive measures in HD clinical trials. We first consider the role of cognition in clinical trial endpoint models, including a review of previous HD clinical trials that have included cognitive measures. We evaluate strategies for selecting cognitive tools for HD clinical trials, and consider cognitive assessments that have been used in other neuropsychiatric disorders, namely Alzheimer disease and schizophrenia. Next, we describe a general framework for selecting patient-based outcomes in clinical trials, and apply this framework to the selection of cognitive outcomes. Using the HD-Cognitive Assessment Battery (HD-CAB), a new cognitive battery designed for clinical trials, we illustrate the evaluation of cognitive outcomes in terms of their responsivity, reliability, validity, appropriateness, precision, interpretability, feasibility, and acceptability. Finally, we articulate a pathway for continued development of cognitive tools that would pave the way for finding treatments that ameliorate cognitive decline in HD.

abstract = "Several Huntington disease (HD) clinical trials are in progress and on the horizon. Potential treatments are increasingly being targeted at ameliorating the cognitive decline in HD. This necessitates a careful consideration of trial designs, including endpoint strategies suitable for testing cognitive function. The aim of this chapter is to evaluate and consider the use of cognitive measures in HD clinical trials. We first consider the role of cognition in clinical trial endpoint models, including a review of previous HD clinical trials that have included cognitive measures. We evaluate strategies for selecting cognitive tools for HD clinical trials, and consider cognitive assessments that have been used in other neuropsychiatric disorders, namely Alzheimer disease and schizophrenia. Next, we describe a general framework for selecting patient-based outcomes in clinical trials, and apply this framework to the selection of cognitive outcomes. Using the HD-Cognitive Assessment Battery (HD-CAB), a new cognitive battery designed for clinical trials, we illustrate the evaluation of cognitive outcomes in terms of their responsivity, reliability, validity, appropriateness, precision, interpretability, feasibility, and acceptability. Finally, we articulate a pathway for continued development of cognitive tools that would pave the way for finding treatments that ameliorate cognitive decline in HD.",

N2 - Several Huntington disease (HD) clinical trials are in progress and on the horizon. Potential treatments are increasingly being targeted at ameliorating the cognitive decline in HD. This necessitates a careful consideration of trial designs, including endpoint strategies suitable for testing cognitive function. The aim of this chapter is to evaluate and consider the use of cognitive measures in HD clinical trials. We first consider the role of cognition in clinical trial endpoint models, including a review of previous HD clinical trials that have included cognitive measures. We evaluate strategies for selecting cognitive tools for HD clinical trials, and consider cognitive assessments that have been used in other neuropsychiatric disorders, namely Alzheimer disease and schizophrenia. Next, we describe a general framework for selecting patient-based outcomes in clinical trials, and apply this framework to the selection of cognitive outcomes. Using the HD-Cognitive Assessment Battery (HD-CAB), a new cognitive battery designed for clinical trials, we illustrate the evaluation of cognitive outcomes in terms of their responsivity, reliability, validity, appropriateness, precision, interpretability, feasibility, and acceptability. Finally, we articulate a pathway for continued development of cognitive tools that would pave the way for finding treatments that ameliorate cognitive decline in HD.

AB - Several Huntington disease (HD) clinical trials are in progress and on the horizon. Potential treatments are increasingly being targeted at ameliorating the cognitive decline in HD. This necessitates a careful consideration of trial designs, including endpoint strategies suitable for testing cognitive function. The aim of this chapter is to evaluate and consider the use of cognitive measures in HD clinical trials. We first consider the role of cognition in clinical trial endpoint models, including a review of previous HD clinical trials that have included cognitive measures. We evaluate strategies for selecting cognitive tools for HD clinical trials, and consider cognitive assessments that have been used in other neuropsychiatric disorders, namely Alzheimer disease and schizophrenia. Next, we describe a general framework for selecting patient-based outcomes in clinical trials, and apply this framework to the selection of cognitive outcomes. Using the HD-Cognitive Assessment Battery (HD-CAB), a new cognitive battery designed for clinical trials, we illustrate the evaluation of cognitive outcomes in terms of their responsivity, reliability, validity, appropriateness, precision, interpretability, feasibility, and acceptability. Finally, we articulate a pathway for continued development of cognitive tools that would pave the way for finding treatments that ameliorate cognitive decline in HD.